Chemotherapy combination drugs for solid tumors

Abstract

This invention relates to a combination chemotherapy drug for solid tumors, comprising any clinically used chemotherapy drug combined with a mitochondrial extract to form the active pharmaceutical ingredient, wherein the mitochondrial extract and the clinically used chemotherapy drug are each an independent drug delivery unit. Experiments of this invention have demonstrated that the combined use of the mitochondrial extract and the chemotherapy drug effectively enhances the drug's efficacy compared to using the chemotherapy drug alone, thereby improving the therapeutic effect of chemotherapy for solid tumors.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology and relates to a combination chemotherapy drug for solid tumors, particularly a drug for treating solid tumors composed of mitochondrial extract and chemotherapy drugs. Background Technology

[0002] In recent decades, with the transformation of disease patterns and the aging of the population, the cancer burden in my country has been increasing, and cancer prevention and control are facing a severe situation. The most common types of cancer are, in order, lung cancer, colon cancer, gastric carcinoma, breast cancer, and liver cancer.

[0003] In clinical practice, the concept of "solid tumor" is frequently mentioned. A solid tumor is a tangible tumor that can be detected through clinical examinations such as X-rays, CT scans, ultrasound, or palpation to form a palpable mass. Solid tumors account for the top five categories of cancer deaths. Furthermore, in recent years, based on the activity of the immune response, tumors have been classified into "cold tumors" and "hot tumors." Hot tumors respond well to immunotherapy due to highly active immune cells, while cold tumors are resistant to immunotherapy due to a lack of immune cell infiltration. Therefore, the treatment of cold tumors has become a significant challenge, but also a hot research topic.

[0004] Lung cancer is often classified into non-small cell lung cancer (NSCLC) and small cell lung cancer, with NSCLC accounting for the vast majority of lung cancer types. Chemotherapy is an indispensable part of lung cancer treatment; clinically, more than 90% of lung cancer patients require chemotherapy, especially those in the middle or late stages or those at high risk of recurrence after surgery. Chemotherapy can significantly prolong survival time and improve quality of life. Currently, platinum-based doublet chemotherapy is still the first choice for NSCLC, using cisplatin as the base combined with another chemotherapy drug, such as etoposide, paclitaxel, docetaxel, or gemcitabine. For non-squamous cell carcinoma patients, pemetrexed combined with cisplatin chemotherapy can be chosen. Chemotherapy regimens for small cell lung cancer patients include cisplatin or carboplatin combined with etoposide, or irinotecan combined with platinum-based drugs.

[0005] Chemotherapy can kill residual tumor cells, reduce the risk of recurrence, inhibit further spread and metastasis of cancer cells, and improve survival rates in patients with intermediate and advanced breast cancer. Common chemotherapy regimens include: 1) anthracycline-based regimens, such as AC: doxorubicin / cyclophosphamide, EC: epirubicin / cyclophosphamide; 2) sequential anthracycline and taxane regimens, such as AC → paclitaxel, AC → docetaxel; 3) combination chemotherapy regimens without anthracyclines, such as the TC regimen: docetaxel / cyclophosphamide. Women with triple-negative breast cancer (TNBC) are characterized by younger age of onset, larger lesions, higher lymph node positivity rates, later clinical stage, higher histological grade, and stronger invasiveness compared to non-TNBC patients. The 3-year recurrence and metastasis rate after initial treatment is 8.11%, and the 5-year recurrence and metastasis rate is 12.98%. This type of breast cancer lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and is not sensitive to traditional endocrine therapy and HER2-targeted therapy. Therefore, the standard treatment for TNBC is still mainly chemotherapy. Single-agent or combination chemotherapy should be rationally selected at different stages of disease development. The preferred drugs are single-agent / combination regimens based on anthracyclines / taxanes / platinum.

[0006] Esophageal cancer is a common malignant tumor of the digestive system. For patients with advanced esophageal cancer and some metastatic esophageal cancer, the recommended first-line radical chemotherapy regimens are fluorouracil + cisplatin, paclitaxel + carboplatin, fluorouracil + oxaliplatin, capecitabine + cisplatin, capecitabine + oxaliplatin, paclitaxel + fluorouracil, etc.

[0007] Liver cancer is the most common type of cancer, with consistently high incidence and mortality rates. In clinical practice, some liver cancer patients do not meet the criteria for targeted therapy and can only rely on chemotherapy. Oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) have been approved in my country for first-line treatment of advanced and metastatic liver cancer that is not suitable for surgical resection or local treatment.

[0008] Currently, the main first-line chemotherapy drugs for gastric cancer in clinical treatment are based on fluorouracil, combined with platinum and / or taxanes to form two- or three-drug regimens. Current CSCO guidelines primarily recommend oxaliplatin plus fluorouracil-based combination therapy.

[0009] Pancreatic cancer is known as the "King of Cancers" due to its insidious onset; approximately 80% of pancreatic cancer patients are already in the locally advanced or metastatic stage at the time of initial diagnosis, with a 5-year overall survival rate of less than 10%. First-line treatment for advanced pancreatic cancer remains chemotherapy, with main regimens including fluorouracil + leucovorin + irinotecan + oxaliplatin, irinotecan liposome + fluorouracil + leucovorin + oxaliplatin, cisplatin + albumin-bound paclitaxel + capecitabine + gemcitabine, gemcitabine combined with albumin-bound paclitaxel, and gemcitabine monotherapy.

[0010] Patients with intermediate to advanced colorectal cancer often require chemotherapy to appropriately prolong their survival, relieve local symptoms, provide surgical opportunities for some patients, reduce the possibility of postoperative recurrence, and extend progression-free survival. Common chemotherapy regimens for colorectal cancer include: FOLFOX regimen (5-FU, leucovorin, oxaliplatin); CAPEOX regimen (oxaliplatin, capecitabine). Other treatment options include capecitabine monotherapy or 5-FU / LV. The 5-year overall survival (OS) for stage II colorectal cancer patients is approximately 58.4%–87.5%.

[0011] Ovarian cancer, due to its insidious onset and lack of obvious symptoms in the early stages, often results in most patients being diagnosed at an advanced stage, leading to a persistently high mortality rate and earning it the title of "King of Gynecological Cancers." However, considering its sensitivity to chemotherapy, chemotherapy remains a crucial treatment option for both newly diagnosed and recurrent ovarian cancer. The median overall survival (OS) after surgical resection of ovarian cancer is approximately 39.4–82.8 months. For most pathological types and stages of ovarian cancer, chemotherapy is essential regardless of whether the tumor has been completely removed surgically. Chemotherapy serves as a consolidation and supplementary treatment to surgical intervention, playing a vital role in the management of ovarian cancer.

[0012] Cervical cancer is the most common gynecological malignancy, ranking fourth in both incidence and mortality among female malignancies. It is estimated that approximately one woman dies from cervical cancer every two minutes worldwide. Common chemotherapy regimens for advanced cervical cancer include cisplatin + paclitaxel, topotecan + paclitaxel, and carboplatin + paclitaxel.

[0013] Osteosarcoma is the most common primary malignant bone tumor and one of the most aggressive and cold-labeled tumors, posing a significant threat to the health of children and adolescents. Treatment both domestically and internationally typically involves a combination of chemotherapy and surgery. Chemotherapy plays a crucial role in osteosarcoma treatment, encompassing preoperative chemotherapy, postoperative chemotherapy, and chemotherapy for metastatic patients. Currently, cisplatin + doxorubicin and high-dose methotrexate + cisplatin + doxorubicin (MAP) are listed as first-line recommended regimens, with a 5-year progression-free survival (PFS) rate of 44% in operable, non-metastatic osteosarcoma patients.

[0014] With the continuous improvement and innovation of research technology, it has become increasingly clear that tumors are a mitochondrial energy metabolism disease, mitochondrial dysfunction is a key cause of tumor development and progression, repairing mitochondrial function may be a key target for tumor treatment, and regulating the body's mitochondrial function through drugs or genetics may be a new way to fight cancer. Summary of the Invention

[0015] The purpose of this invention is to provide a combination chemotherapy drug for solid tumors, which utilizes mitochondrial extract to enhance the efficacy of chemotherapy drugs and provide a more effective treatment for solid tumors.

[0016] This invention has found that, compared to the use of chemotherapy drugs alone, the combined use of mitochondrial extract and chemotherapy drugs can effectively enhance the efficacy of chemotherapy drugs.

[0017] Therefore, the present invention first provides a combination chemotherapy drug for solid tumors, wherein the combination drug is composed of any clinical chemotherapy drug and mitochondrial extract to form the active pharmaceutical ingredient, and the mitochondrial extract and the clinical chemotherapy drug are each an independent drug delivery unit.

[0018] Furthermore, the combination chemotherapy drug for solid tumors described in this invention can also be composed of any one or more clinical chemotherapy drugs combined with mitochondrial extract to form the active pharmaceutical ingredient. Similarly, the mitochondrial extract and the one or more clinical chemotherapy drugs each become an independent drug delivery unit.

[0019] The clinically used chemotherapy drugs mentioned herein can be any drugs currently used in clinical practice for the chemotherapy treatment of various solid tumors, and this invention does not limit them in any way. Furthermore, the clinically used chemotherapy drugs may include, but are not limited to, any one of cisplatin, carboplatin, oxaliplatin, docetaxel, pemetrexed, etoposide, gemcitabine, capecitabine, paclitaxel, fluorouracil, irinotecan, topotecan, doxorubicin, methotrexate, leucovorin, doxorubicin, epirubicin, or cyclophosphamide, or a combination of several of these.

[0020] Furthermore, the solid tumors described in this invention are selected from various clinically confirmed solid tumors such as lung cancer, esophageal cancer, liver cancer, gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, ovarian cancer, cervical cancer, or osteosarcoma.

[0021] This invention validates the effects of mitochondrial extract on the efficacy of chemotherapy drugs in several types of solid tumors with high mortality rates and cold tumors with high malignancy, including lung cancer, breast cancer, triple-negative breast cancer, colon cancer, osteosarcoma, and ovarian cancer. Through in vitro and in vivo experiments, it has been demonstrated that mitochondrial extract can enhance the killing ability of chemotherapy drugs on malignant solid tumor cells, thereby improving the efficacy of chemotherapy.

[0022] Furthermore, the preferred dosage of the mitochondrial extract used in this invention is 10 8 ~10 11 One mitochondria.

[0023] Furthermore, the present invention also provides a combination chemotherapy drug, which uses a clinically used chemotherapy drug as the active ingredient and combines it with a mitochondrial extract to improve the efficacy of the clinically used chemotherapy drug.

[0024] Furthermore, the present invention also provides the use of the aforementioned combination chemotherapy drug in the preparation of a medicament for treating solid tumors.

[0025] This invention utilizes mitochondrial extract in combination with various clinical chemotherapy drugs for different solid tumors, verifying that the combined use of mitochondrial preparations and chemotherapy drugs can enhance the efficacy of chemotherapy drugs. This invention makes a beneficial exploration to improve the effectiveness of chemotherapy drugs for patients with advanced solid tumors, and reduce the mental stress and socioeconomic burden on patients and their families. Attached Figure Description

[0026] Figure 1 Mitochondrial extract enhances the killing effect of cisplatin on lung cancer cells A549.

[0027] Figure 2 The mitochondrial extract enhances the inhibitory effect of docetaxel on tumors.

[0028] Figure 3 Mitochondrial extract enhances the efficacy of chemotherapy combined with pemetrexed and cisplatin.

[0029] Figure 4 Mitochondrial extract enhances the killing effect of cisplatin on MCF-7 breast cancer cells.

[0030] Figure 5 Mitochondrial extract enhances the killing effect of paclitaxel on triple-negative breast cancer cells MDA-MB-231.

[0031] Figure 6 Mitochondrial extract enhances the killing effect of cisplatin on triple-negative breast cancer cells MDA-MB-231.

[0032] Figure 7 The mitochondrial extract enhances the killing effect of 5-FU on HCT116 colon cancer cells.

[0033] Figure 8 The mitochondrial extract enhances the killing effect of cisplatin on osteosarcoma cells MG63.

[0034] Figure 9 Mitochondrial extract enhances the killing effect of cisplatin on Skov3 ovarian cancer cells. Implementation

[0035] The specific embodiments of the present invention will be further described in detail below with reference to the accompanying drawings and examples. The following examples are only used to more clearly illustrate the technical solutions of the present invention, so that those skilled in the art can better understand and utilize the present invention, and are not intended to limit the scope of protection of the present invention.

[0036] Unless otherwise specified, the production processes, experimental methods, or testing methods involved in the embodiments of this invention are all conventional methods in the prior art, and their names and / or abbreviations are all conventional names in the field, which are very clear and distinct in the relevant application areas. Those skilled in the art can understand the conventional process steps based on the names and apply the corresponding equipment, and implement them according to conventional conditions or the conditions recommended by the manufacturer.

[0037] The various instruments, equipment, raw materials or reagents used in the embodiments of this invention are not subject to any special restrictions on their source. They are all conventional products that can be purchased through regular commercial channels and can be prepared according to conventional methods known to those skilled in the art. Example

[0038] Example 1

[0039] In histopathology, lung cancer is divided into two main types: small cell lung cancer and non-small cell lung cancer. Non-small cell lung cancer accounts for about 85% of all lung cancer cases and can be further divided into squamous cell carcinoma, adenocarcinoma, large cell carcinoma and other subtypes.

[0040] In clinical practice, docetaxel is often chosen to treat patients with squamous cell carcinoma, adenocarcinoma, and non-squamous non-adenocarcinoma of the lung, while pemetrexed combined with cisplatin is often used to treat patients with adenocarcinoma of the lung.

[0041] In this embodiment, C57 / BL6 tumor-bearing mice were used in animal experiments. Two chemotherapy methods were applied to correspond to chemotherapy regimens for different types of lung cancer patients in clinical practice, in order to fully verify that mitochondrial transplantation can improve the efficacy of chemotherapy for lung cancer.

[0042] 1. Mitochondrial extract enhances the killing effect of cisplatin (DDP) on lung cancer cells A549.

[0043] Figure 1 (A) Different concentrations of cisplatin were used to treat lung cancer cells A549. Cell viability was calculated after 24 hours. The results showed that the half-maximal inhibitory concentration (IC50) of cisplatin on the activity of lung cancer cells A549 within 24 hours was 44.3 μM (IC50). 50 =44.3μM).

[0044] Furthermore, intervention with 40 μM cisplatin alone served as the control group, while intervention with 40 μM cisplatin and 1×10 7 The combined intervention with mitochondrial extract ( / mL) was used as the experimental group to investigate the effect of mitochondrial extract combined with cisplatin intervention on the proliferation ability of lung cancer cells A549.

[0045] Figure 1 The results of experiments (B) and (C) showed that after 24 hours of intervention with 40 μM cisplatin alone, the cell viability of A549 cells decreased to 44.01 ± 3.37%, and the inhibition rate of cell proliferation was 55.99 ± 3.37%; however, when combined with 1 × 107 After 24 hours of combined intervention with mitochondrial extract, the cell viability of A549 cells further decreased to 29.62±2.34% (P<0.01), while the inhibition rate of cell proliferation increased to 70.38±2.34% (P<0.01), meaning that the efficacy of mitochondrial extract against cisplatin was improved by 14.39%±5.11%.

[0046] 2. Mitochondrial extract enhances the inhibitory effect of docetaxel (DTX) on lung cancer.

[0047] Six-week-old C57 / BL6 mice were divided into four groups: control group, mitochondrial extract group, docetaxel group, and mitochondrial extract and docetaxel combination group (Mito+DTX group).

[0048] 1.2 × 10⁻⁶ mg / L was subcutaneously injected into the right shoulder and back of the mouse. 6 One week after the LLC cells reached the logarithmic growth phase and the tumor was about the size of a soybean, intervention began.

[0049] The control group received no intervention; the Mito and Mito+DTX groups received tail vein injections of mitochondria (extracted from AC16 cardiomyocytes) twice a week, with a single injection of 1×10⁻⁶. 7 Individuals / animal; DTX group and Mito+DTX group received intraperitoneal injection of docetaxel (10 mg / kg) once a week.

[0050] The experiment was terminated two weeks after the intervention, and tumor size and body weight were observed in each group. Figure 2 (A) shows the tumor size statistics of mice in each group two weeks after chemotherapy, (B) provides a line graph of tumor growth of mice in each group, and (C) shows a line graph of body weight of mice in each group. In the figure, # and P < 0.05 are both P.

[0051] Figure 2 The results showed that all groups inhibited tumor growth compared to the Control group. The inhibition rate of the Mito group was 35.49%, the inhibition rate of the DTX group was 43.49%, and the inhibition rate of the Mito+DTX combination group was 71.03%. The inhibition effect of the Mito+DTX group was the most significant, which was 63.3% higher than that of the DTX group (P<0.05). There was no significant difference in the body weight of mice in each group, which proved that the mitochondrial extract enhanced the inhibitory effect of docetaxel on lung tumors.

[0052] 3. Mitochondrial extract enhances the inhibitory effect of pemetrexed combined with cisplatin (Pem+DDP) on lung cancer.

[0053] Six-week-old C57 / BL6 mice were divided into two groups: the pemetrexed plus cisplatin chemotherapy group (Pem+DDP) and the pemetrexed plus cisplatin chemotherapy plus mitochondrial extract treatment group (Pem+DDP+Mito).

[0054] 1.2 × 10⁻⁶ mg / L was subcutaneously injected into the right shoulder and back of the mouse. 6 One week after the LLC cells reached the logarithmic growth phase and the tumor was about the size of a soybean, intervention began.

[0055] The Pem+DDP+Mito group received tail vein injections of mitochondria (extracted from AC16 cardiomyocytes) twice a week, with each injection containing 2×10⁻⁶ mitochondria. 7 Each animal was injected once a week with pemetrexed (80 mg / kg) and twice a week with cisplatin (5 mg / kg).

[0056] The experiment was terminated two weeks after the intervention, and tumor size and body weight were observed in each group. Figure 3 (A) shows the gross image of the tumor in each group of mice, (B) shows the line graph of tumor growth in each group of mice, (C) shows the tumor size statistics in each group of mice two weeks after chemotherapy, and (D) shows the line graph of body weight in each group of mice.

[0057] Compared with the previous Control group, the tumor inhibition rate of the Pem+DDP group was 47.3%, while the tumor inhibition rate of the Pem+DDP+Mito group was increased to 76.1%; the tumor inhibition rate of the Pem+DDP+Mito group was 60.9% higher than that of the Pem+DDP group (P<0.01), and there was no statistically significant difference in the body weight of mice in each group, demonstrating that mitochondrial extract improves the chemotherapy efficacy of pemetrexed combined with cisplatin.

[0058] Example 2

[0059] 1. Mitochondrial extract enhances the efficacy of cisplatin in treating breast cancer.

[0060] Figure 4 (A) Different concentrations of cisplatin were used to treat MCF-7 breast cancer cells. Cell viability was calculated after 48 hours. The results showed that the half-maximal inhibitory concentration (IC50) of cisplatin on the activity of MCF-7 breast cancer cells within 48 hours was 2.0 μM. 50 =2.0μM).

[0061] Furthermore, intervention with 2 μM cisplatin alone served as the control group, while intervention with 2 μM cisplatin and 1×10 7 The combined intervention with mitochondrial extract ( / mL) was used as the experimental group to investigate the effect of mitochondrial extract combined with cisplatin intervention on the proliferation ability of breast cancer cells MCF-7.

[0062] Figure 4The results of experiments (B) and (C) showed that after 48 hours of intervention with 2 μM cisplatin alone, the cell viability of MCF-7 cells decreased to 43.51 ± 3.46%, and the inhibition rate of cell proliferation was 56.49 ± 3.46%; however, when combined with 1 × 10⁻⁶ cisplatin... 7 After 48 hours of combined intervention with mitochondrial extract, the cell viability of MCF-7 cells further decreased to 34.15±0.81% (P<0.01), while the inhibition rate of cell proliferation increased to 65.85±0.81% (P<0.01), meaning that the efficacy of mitochondrial extract against cisplatin was improved by 9.36%±2.05%.

[0063] 2. Mitochondrial extract enhances the efficacy of paclitaxel in triple-negative breast cancer.

[0064] Figure 5 (A) Triple-negative breast cancer cells MDA-MB-231 were treated with different concentrations of paclitaxel. Cell viability was calculated after 48 hours. The results showed that the half-maximal inhibitory concentration (IC50) of paclitaxel on the activity of MDA-MB-231 triple-negative breast cancer cells within 48 hours was 3.5 μM (IC50). 50 =3.5μM).

[0065] Furthermore, intervention with 2 μM paclitaxel alone served as the control group, while 2 μM paclitaxel was used in combination with 1×10 7 The combined intervention with mitochondrial extract ( / mL) was used as the experimental group to investigate the effect of mitochondrial extract combined with paclitaxel intervention on the proliferation of triple-negative breast cancer cells MDA-MB-231.

[0066] Figure 5 The results of experiments (B) and (C) showed that after intervention with 2 μM paclitaxel alone for 48 h, the cell viability of MDA-MB-231 decreased to 50.4 ± 2.71%, and the inhibition rate of cell proliferation was 49.6 ± 2.71%; however, when it was combined with 1 × 10 7 After 48 hours of combined intervention with mitochondrial extract, the cell viability of MDA-MB-231 cells further decreased to 37.19±0.71% (P<0.01), while the inhibition rate of cell proliferation increased to 62.81±0.71% (P<0.01), indicating that the efficacy of mitochondrial extract against paclitaxel was improved by 13.20%±1.618%.

[0067] 3. Mitochondrial extract enhances the efficacy of cisplatin in triple-negative breast cancer.

[0068] Figure 6(A) Triple-negative breast cancer cells MDA-MB-231 were treated with different concentrations of cisplatin. Cell viability was calculated after 48 hours. The results showed that the half-maximal inhibitory concentration (IC50) of cisplatin on the activity of MDA-MB-231 triple-negative breast cancer cells within 48 hours was 2.0 μM (IC50). 50 =2.0μM).

[0069] Furthermore, intervention with 2 μM cisplatin alone served as the control group, while intervention with 2 μM cisplatin and 1×10 7 The combined intervention with mitochondrial extract ( / mL) was used as the experimental group to investigate the effect of mitochondrial extract combined with cisplatin intervention on the proliferation of triple-negative breast cancer cells MDA-MB-231.

[0070] Figure 6 The results of experiments (B) and (C) showed that after 48 hours of intervention with 2 μM cisplatin alone, the cell viability of MDA-MB-231 decreased to 63.33 ± 7.67%, and the inhibition rate of cell proliferation was 36.67 ± 7.67%; however, when it was combined with 1 × 10 7 After 48 hours of combined intervention with mitochondrial extract, the cell viability of MDA-MB-231 cells further decreased to 48.84±4.12% (P<0.01), while the inhibition rate of cell proliferation increased to 51.16±4.12% (P<0.01), indicating that the efficacy of mitochondrial extract against cisplatin was improved by 14.49%±5.03%.

[0071] Example 3

[0072] Mitochondrial extract enhances the efficacy of 5-FU against colon cancer.

[0073] Figure 7 (A) Different concentrations of 5-FU were used to treat HCT116 colon cancer cells. Cell viability was calculated after 24 hours. The results showed that the half-maximal inhibitory concentration (IC50) of 5-FU on the activity of HCT116 colon cancer cells within 24 hours was 21.7 μM. 50 =21.7μM).

[0074] Intervention with 25 μM 5-FU alone served as the control group, while intervention with 25 μM 5-FU and 1×10 7 The combined intervention with mitochondrial extract ( / mL) was used as the experimental group to investigate the effect of mitochondrial extract combined with 5-FU intervention on the proliferation ability of HCT116 colon cancer cells.

[0075] Figure 7 The results of experiments (B) and (C) showed that after 24 hours of intervention with 25 μM 5-FU alone, the cell viability of HCT116 decreased to 44.97 ± 3.10%, and the inhibition rate of cell proliferation was 55.03 ± 3.10%; however, when it was combined with 1 × 107 After 24 hours of combined intervention with mitochondrial extract, the cell viability of HCT116 cells further decreased to 31.36±0.79% (P<0.01), while the inhibition rate of cell proliferation increased to 68.63±0.79% (P<0.01), meaning that the efficacy of mitochondrial extract against 5-FU was improved by 13.61%±3.62%.

[0076] Example 4

[0077] Mitochondrial extract enhances the efficacy of cisplatin in treating osteosarcoma.

[0078] Figure 8 In the study (A), osteosarcoma cells MG63 were treated with different concentrations of cisplatin. After 24 hours, cell viability was calculated, and the half-maximal inhibitory concentration (IC50) of cisplatin on the activity of osteosarcoma cells MG63 was found to be 9.568 μg / mL. 50 =9.568μg / mL).

[0079] The control group received intervention with 8 μg / mL cisplatin alone, while the control group received 8 μg / mL cisplatin and 1×10 7 The combined intervention with mitochondrial extract ( / mL) was used as the experimental group to investigate the effect of mitochondrial extract combined with cisplatin intervention on the proliferation ability of osteosarcoma cells MG63.

[0080] Figure 8 The results of experiments (B) and (C) showed that after 24 hours of intervention with 8 μg / mL cisplatin alone, the cell viability of MG63 cells decreased to 63.84±1.35%, and the inhibition rate of cell proliferation was 36.16±1.35%; while when combined with 1×10 7 After 24 hours of combined intervention with mitochondrial extract, the cell viability of MG63 cells further decreased to 48.29±6.84% (P<0.01), while the inhibition rate of cell proliferation increased to 51.71±6.84% (P<0.01), meaning that the efficacy of mitochondrial extract against cisplatin was improved by 15.55%±4.02%.

[0081] Example 5

[0082] Mitochondrial extract enhances the efficacy of cisplatin in treating ovarian cancer.

[0083] Within 48 hours, the half-maximal inhibitory concentration (IC50) of cisplatin against the activity of Skov3 ovarian cancer cells was 12.6 μM (IC50). 50 =12.6μM), such as Figure 9 (A). Intervention with 15 μM cisplatin alone served as the control group; 15 μM cisplatin was used in combination with 1×10⁻⁶ cisplatin. 7 The combined intervention with mitochondrial extract ( / mL) was used as the experimental group to investigate the effect of mitochondrial extract combined with cisplatin intervention on the proliferation ability of Skov3 ovarian cancer cells.

[0084] Figure 9 Results (B) and (C) showed that after 48 hours of intervention with 15 μM cisplatin alone, the cell viability of Skov3 cells decreased to 55.02 ± 5.0%, and the inhibition rate of cell proliferation was 44.98 ± 5.0%; when combined with 1 × 10⁻⁶ cisplatin... 7 After 48 hours of combined intervention with mitochondrial extract, the cell viability of Skov3 cells decreased to 30.64±2.06% (P<0.01), while the inhibition rate of cell proliferation increased to 69.36±2.06% (P<0.01), indicating that the efficacy of mitochondrial extract against cisplatin was improved by 24.39%±3.48%.

[0085] The above embodiments of the present invention do not describe all details exhaustively, nor do they limit the present invention to the embodiments described above. Various changes, modifications, substitutions, and variations made by those skilled in the art to these embodiments without departing from the principles and spirit of the present invention should be included within the scope of protection of the present invention.

Claims

1. A combination chemotherapy drug for solid tumors, comprising any clinically used chemotherapy drug and a mitochondrial extract as the active pharmaceutical ingredient, wherein the mitochondrial extract and the clinically used chemotherapy drug are each an independent drug delivery unit.

2. A combination chemotherapy drug for solid tumors, comprising any one or more clinically used chemotherapy drugs and mitochondrial extract as the active pharmaceutical ingredient, wherein the mitochondrial extract and the one or more clinically used chemotherapy drugs are each independent drug delivery units.

3. The combined drug according to claim 1 or 2, wherein the dosage of the mitochondrial extract is 10 8 ~10 11 One mitochondria.

4. The combination drug according to claim 1 or 2, wherein the clinically used chemotherapy drug is cisplatin, carboplatin, oxaliplatin, docetaxel, pemetrexed, etoposide, gemcitabine, capecitabine, paclitaxel, fluorouracil, irinotecan, topotecan, doxorubicin, methotrexate, leucovorin calcium, doxorubicin, epirubicin, or cyclophosphamide.

5. The combination drug according to claim 1 or 2, wherein the solid tumor is selected from lung cancer, esophageal cancer, liver cancer, gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, ovarian cancer, cervical cancer, or osteosarcoma.

6. A combination chemotherapy drug, using a clinically used chemotherapy drug as an active ingredient, and using it in combination with a mitochondrial extract to enhance the efficacy of the clinically used chemotherapy drug.

7. The use of the combination chemotherapy drug of claim 6 in the preparation of a medicament for treating solid tumors.

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